Howles C M
Reproductive Health, Ares-Serono International S.A., 15 Bis, Chemin des Mines, 1202, Geneva, Switzerland.
Mol Cell Endocrinol. 2000 Mar 30;161(1-2):25-30. doi: 10.1016/s0303-7207(99)00219-1.
Human gonadotrophin preparations have been used in the treatment of infertility for almost four decades. The earliest preparations were derived from urine from postmenopausal women and contained approximately equal amounts of follicle stimulating hormone (FSH) and luteinizing hormone (LH) activities. However, with the recognition that FSH is the principal regulator of follicular growth and maturation, these have been largely superseded by highly purified urinary FSH preparations and, more recently, recombinant human FSH (r-hFSH). Because of its complexity, r-hFSH is expressed in mammalian cells grown in culture and, from a manufacturing stand point, offers superior purity and batch-to-batch consistency, compared with urinary preparations. A number of clinical trials have compared the efficacy of r-hFSH and urinary FSH in women undergoing assisted reproductive technologies (ART). In general, these have shown that fewer FSH ampoules are required to achieve ovarian stimulation with r-hFSH, while the number of oocytes retrieved and embryos produced are higher than with urinary FSH. Additionally, the results of a recent meta-analysis have also shown that the clinical pregnancy rate per cycle started is significantly higher with r-hFSH, compared with urinary FSH. Furthermore, in poor responder patients, higher implantation rates were seen in patients treated with r-hFSH than in those treated with urinary FSH, suggesting that embryo viability is increased following use of the recombinant preparations. The finding that FSH preparations produce effective ovarian stimulation compared to human menopausal gonadotrophins in women undergoing ART raises the question of whether LH is required for ovarian stimulation. This has been investigated in a number of recent studies. For example, results have suggested that implantation rates may actually be lower in women who received exogenous LH. Such studies suggest, therefore, that in normogonadotrophic women, the addition of LH to an r-hFSH regimen does not add any further clinical benefit and may actually be detrimental. Hence, it appears that LH administration is necessary only in women with hypogonadotrophic hypogonadism. In conclusion, r-hFSH is a consistently pure and high quality gonadotrophin preparation and contributes to increasing the successful outcome of an ART cycle. Together with careful auditing of routine clinical practice, and the application of evidence-based medicine to facilitate clinical decision making, this means that a total quality management approach can be applied to optimize the outcome of assisted reproduction.
人促性腺激素制剂用于治疗不孕症已有近四十年的历史。最早的制剂源自绝经后妇女的尿液，含有大致等量的促卵泡生成素（FSH）和促黄体生成素（LH）活性。然而，随着人们认识到FSH是卵泡生长和成熟的主要调节因子，这些制剂在很大程度上已被高纯度尿FSH制剂以及最近的重组人FSH（r-hFSH）所取代。由于其复杂性，r-hFSH在培养的哺乳动物细胞中表达，从生产角度来看，与尿制剂相比，它具有更高的纯度和批次间一致性。多项临床试验比较了r-hFSH和尿FSH在接受辅助生殖技术（ART）的女性中的疗效。总体而言，这些试验表明，使用r-hFSH实现卵巢刺激所需的FSH安瓿数量更少，而回收的卵母细胞数量和产生的胚胎数量高于使用尿FSH时。此外，最近一项荟萃分析的结果还表明，与尿FSH相比，使用r-hFSH开始每个周期的临床妊娠率显著更高。此外，在反应不良的患者中，使用r-hFSH治疗的患者的着床率高于使用尿FSH治疗的患者，这表明使用重组制剂后胚胎活力增加。在接受ART的女性中，与人类绝经期促性腺激素相比，FSH制剂能产生有效的卵巢刺激，这一发现引发了是否需要LH进行卵巢刺激的问题。最近的一些研究对此进行了调查。例如，结果表明接受外源性LH的女性的着床率实际上可能更低。因此，此类研究表明，在正常促性腺激素水平的女性中，在r-hFSH方案中添加LH不会带来任何进一步的临床益处，实际上可能有害。因此，似乎只有在低促性腺激素性性腺功能减退的女性中才需要给予LH。总之，r-hFSH是一种始终保持纯净且高质量的促性腺激素制剂，有助于提高ART周期的成功率。连同对常规临床实践的仔细审核，以及应用循证医学来促进临床决策，这意味着可以应用全面质量管理方法来优化辅助生殖的结果。
